Examination of Multiple Medication Use Among TRICARE Beneficiaries Aged 65 Years and Older

BACKGROUND: The simultaneous use of multiple prescription medications has been associated with an increased risk of adverse drug events and other drug-related complications, especially in the elderly. OBJECTIVES: To quantify the prevalence of use of multiple medications among a sample of Department of Defense (DoD) health care beneficiaries, aged 65 years and older, who used their TRICARE (military health care services) benefit to obtain prescription medication. METHODS: Outpatient pharmacy fill records were analyzed for a 10% random sample of 1.27 million TRICARE beneficiaries aged 65 years and older who obtained 1 or more prescription medications in the 90-day period from December 1, 2004, through February 28, 2005. The First DataBank generic code number was used to identify drugs and to calculate the mean number of medications obtained and the mean, frequency, and type of American Hospital Formulary System drug therapy categories. Statistical significance for gender and age subgroups was tested via independent tests. RESULTS: There were 1,268,162 users of the TRICARE pharmacy benefit in the 90-day study period from December 1, 2004, through February 28, 2005, approximately 72.7% of 1,744,072 eligible beneficiaries. The 10% sample of these users (n=126,682) accounted for 1,091,699 pharmacy fill records for 761,043 unique medications, or an average of 6.01 [SD ± 4.01] unique medications per user, distributed across an average of 3.80 [±2.08] therapeutic categories; 8.8% of users received 1 medication, 50.0% received 5 or more medications from an average of 3 therapeutic categories, and 2.8% obtained 16 or more medications from an average of 8 therapeutic categories. Multiple drug use was more prevalent among women relative to men, with an average of 6.28 [±4.12] medications from 4.03 [±2.11] therapeutic categories for women versus an average of 5.69 [±3.85] medications from an average of 3.80 [±2.08] therapeutic categories for men (P less than 0.001). The prevalence of multiple drug use peaked among beneficiaries aged 80 to 84 years. Cardiovascular drugs, central nervous system agents, and hormones and synthetic substitutes were the 3 most common therapeutic categories used by 77%, 48%, and 42% of beneficiaries, respectively. CONCLUSIONS: This baseline analysis documented the common use of multiple medications among TRICARE beneficiaries. The DoD faces a challenge similar to that of Medicare Part D drug plans to cost-effectively monitor and optimize pharmacotherapy for its older beneficiaries.

was assessed. 9 A number of studies estimate the percentage of their study populations at elevated risk of an adverse drug interaction or other adverse drug event based on the size or composition of the subject' s medication list, but the extent to which potential drug interactions actually occur or the clinical significance of some recognized drug interactions is somewhat disputed. [10][11][12] No clear standard has emerged regarding the number of medications that may safely be used together, but there is compelling evidence that the potential for adverse drug events, including drug-drug interactions, drug-nondrug interactions, drug-disease interactions, adverse side effects, and medication noncompliance, increases with the number of medications being used, and many of these events may be preventable. 2,13,14 We examined the prevalence of multiple medication use among a 10% sample of 1.27 million Department of Defense (DoD) TRICARE (military health care services) beneficiaries, aged 65 years and older, who used their TRICARE benefit to obtain prescription medication. The TRICARE pharmacy benefit is available to all DoD beneficiaries in all locations, including retired service members, their spouses, and other dependents, and dependents of deceased service members (older veterans will be eligible under TRICARE only if they completed a full military career before retiring from service). Beneficiaries need only a valid DoD identification card and a prescription to use the benefit.
At the time of this study, prescriptions could be filled at military pharmacies at no cost or through a mail-order or a network community pharmacy with a $3 copayment for generic or $9 copayment for brand medications. Beneficiaries could also fill prescriptions at a nonnetwork community pharmacy, with the potential for a point-of-service deductible and higher copayment, though this option was not frequently used by beneficiaries aged 65 years and older. TRICARE does not impose premiums, enrollment fees, benefit caps, or plan-wide deductibles that increase the patient' s cost burden beyond the point-of-service copayment amount, or otherwise promote periods of potential noncoverage. 15,16 Beneficiaries could use their prescription drug benefit without using any other health care services offered under TRICARE, and TRICARE was a secondary payer if other health insurance was used to purchase prescription medication. 17 The purpose of the current research was to quantify and characterize multiple medication use among the DoD beneficiaries aged 65 years and older with the ultimate goal of assessing the need for additional interventions to mitigate risks posed to older adults by the growing role of pharmacotherapy in their treatment regimen.

ss Methods
The DoD maintains an enterprise-wide information system that captures patient demographic and prescription information for each prescription filled by a beneficiary using the TRICARE pharmacy benefit. A fill record is created in real-time when the prescription is filled regardless of whether a military, community, or mail-order pharmacy is used. The fill records are forwarded to a central data repository and processed for data validity and consistency, such as the removal of transactions that have been reversed (e.g., prescriptions that were filled but never picked up) and the coding of a unique patient identifier that enables the matching of patient-level data with other DoD administrative systems.
Since the TRICARE drug benefit allows beneficiaries to obtain a maximum 90-day supply of medication at a time, 90 days was the shortest period of time that allowed us to obtain a snapshot of drug use among the study population while minimizing the impact of 1-time medication fills and changes in medication dosing on our estimates of the number of medications obtained. A census of outpatient pharmacy fill records for beneficiaries aged 65 years and older for a 90-day period (December 1, 2004, through February 28, 2005) was extracted from this central repository in July 2005, resulting in a total of 11,390,888 fill records.
A total of 5.5% of fill records were then excluded from the dataset on the basis of missing data (such as missing person or product identifier), clinician-administered prescriptions, or nondrug items, yielding a net of 10,768,945 fill records. These fill records were aggregated into patient-level records for 1,268,162 unique beneficiaries that included all prescriptions filled for each beneficiary during the study period. In order to reduce the computing resources required for analysis of a population of this size, we selected a 10% random subsample of beneficiaries for analysis. A 10% subsample ensured that our findings were representative of the study population within a 99.5% confidence level. The final dataset included 1,091,699 pharmacy fill records, corresponding to 761,043 unique medications dispensed to 126,682 beneficiaries.
The First DataBank generic code number (GCN) was used to define unique medications, and the level 1 (2-digit) American Hospital Formulary System (AHFS) nomenclature was used to define therapeutic categories. The level 1 therapeutic category represents the highest level of AHFS categorization and comprises a total of 30 categories, one of which is a placeholder category for new medications that have not yet been permanently placed in the AHFS nomenclature (therapeutic category 92, Unclassified Agents). Therapeutic categories were ranked by number and frequency of beneficiary use, and the mean number of medications obtained per beneficiary within each therapeutic category was calculated.
The mean number of medications obtained and therapeutic categories used were calculated by beneficiary gender and age group. The distributions of beneficiaries by the total number of medications obtained and therapeutic categories used within the 90-day study period were constructed and analyzed. The statistical significance of differences between subgroups was assessed using independent t tests using SPSS, Base 10.0.

ss Results
Overall, 72.7% of eligible TRICARE beneficiaries aged 65 years and older used their TRICARE benefit to obtain prescription medication during the 90-day study period ( Table 1). The frequencies of men and women using their pharmacy benefit were 69.3% and 75.9%, respectively. Pharmacy benefit use ranged from 72.5% to 73.9% in the 80 to 84-year age group, but dropped to 66.6% among beneficiaries aged 85 years and older. Approximately 95.5% of TRICARE pharmacy benefit users used other TRICARE health care services in the 9 months preceding the study period, the majority of which (90%) obtained most or all of their care through civilian providers (data not presented). The remaining 4.5% of TRICARE pharmacy beneficiaries who did not use their TRICARE health services benefit either used no services or obtained health care services through another health plan.
The number and percentage of beneficiaries in the sample population who obtained 1 or more medications in each therapeutic category are presented in Table 2. Cardiovascular drugs (24) were used by 77.0% of the beneficiaries aged 65 years and older who filled a prescription during the study period. Most frequently obtained cardiovascular medications were (in descending order) statins, renin-angiotensin system inhibitors, beta-blockers, and calcium channel blockers. Central nervous system agents (28) were obtained by 47.7% of beneficiaries and included primarily anti-inflammatories, pain relief medications, and antidepressants. Hormones and synthetic substitutes (68) were obtained by 41.8% of the sample population and included antidiabetic and thyroid medications. These 3 therapeutic categories were also associated with the highest mean number of medications obtained per beneficiary, 2.27 (±1.31) for cardiovascular medications, 1.93 (±1.34) for central nervous system agents, and 1.54 (±0.83) for hormones and synthetic substitutes.
Approximately 31% of beneficiaries obtained medications in each of the following categories: gastrointestinal drugs (56); anti-infective agents (8); or electrolytic, caloric, and water balance agents (40). A total of 28.6% of beneficiaries obtained unclassified therapeutic agents (92), which are medications that have not been permanently placed in the AHFS nomenclature. This percentage corresponded to 42,205 of the 761,043 (5.5%) of the unique medications obtained by the sample population during the study period and included primarily brand medications for treatment of osteoporosis, enlarged prostate, gout, asthma, and seasonal allergies, as well as anticlotting agents. Each of the remaining therapeutic categories was used by less than 20% of the beneficiary population.
The mean number of individual medications obtained across all therapeutic categories and the mean number of therapeutic categories used, by gender and age group, are presented in Table 3. Overall, the sample population obtained a mean of 6.01 (±4.01) medications from a mean of 3.80 (±2.08) therapeutic categories during the 90-day study period (refills excluded). Both the mean number of medications obtained and the therapeutic categories used were significantly higher among women relative to men within each age group and increased significantly for both men and women with increasing age up to the age of 85 years.
The number, percentage, and cumulative percentage of beneficiaries and the mean number of therapeutic categories used relative to the number of medications obtained during the study period are presented in Table 4. A total of 11,128   Figure 1. The distribution of beneficiaries by number of therapeutic categories used during the study period is graphically presented in Figure 2. A total of 16,533 beneficiaries (13.1%) in the study population used only 1 therapeutic category, and 3,192 beneficiaries (2.5%) used 9 or more therapeutic categories during the 90-day study period. The median and mode of the distribution occurred at 3 therapeutic categories (tabular data not presented).

ss Discussion
Our findings present a snapshot of the frequency and type of multiple-medication use among a sample of older adults aged 65 years and older. From a 10% sample of the 1.27 million DoD health care beneficiaries who used their TRICARE pharmacy benefit during the 90-day study period, half obtained 5 or more medications concomitantly from a mean of 3 therapeutic categories, and 2.8% obtained 16 or more prescription medications from a mean of 8 therapeutic categories. Prior studies among the elderly found that the risk of an adverse drug event exceeded 50% with the concomitant use of 5 or more medications, suggesting that some form of intervention might be warranted for those beneficiaries at the higher end of the use spectrum. 2,13 We found that medication use generally increased with increasing patient age but peaked among the 80-to-84-year-olds. The rate of increase was gradual because of the relatively high medication use by the youngest age group examined, 65-to-69-year-olds, with means of 5.2 and 6.0 medications and 3.3 and 3.9 therapeutic categories for men and women, respectively. This finding is consistent with other studies that found prescription medication use for many older adults began before age 65. 18 The standard error for the mean number of prescriptions and therapeutic categories used, however, indicates a wide and relatively similar variation in pharmaceutical use within all age groups. We found

Examination of Multiple Medication Use Among TRICARE Beneficiaries Aged 65 Years and Older
that women, on average, obtained 10% more prescription medications than men. This finding is consistent with other studies that found medication use by women exceeded that of men by 9% to 26%. 9,19 Our estimates of the number of prescription medications being used by the study population generally exceeded those of previous studies of U.S. populations, but direct comparison of findings was complicated by the absence of a standard method for assessing medication use. A 1987 chart review of ambulatory patients in Kentucky, aged 60 years and older, found that 32% took 5 or more prescription medications concurrently, with a mean of 3.75 and 4.22 prescription medications for men and women, respectively. 12 A 1995 claims-based study of Medicare-eligible beneficiaries aged 65 years and older in Texas found that 23% received 6 or more prescription medications during a 3-month period. 20 A 1999 claims-based study of New England veterans reported that a mean of 3.54 prescription medications were used by patients over a 6-month period. 21 A 1999 national survey of ambulatory adults reported that 23% of the adults aged 65 years and older used 5 or more prescription medications over a 7-day study period. 22 The estimates reported in studies of non-U.S. populations varied as well. 9 A 1997 study of long-term prescription drug use (>240 days) in the Netherlands found that 42% of elderly patients used 2 or more medications and 4% used 5 or more medications concomitantly on a long-term basis. 23 A surveybased study in Finland found that concomitant use of 6 or more medications increased from 19% of the community-dwelling population aged 64 years or older in 1990-1991 to 25% in 1998-1999. 24 A Danish study of prescription data found that two thirds of all prescription medication users older than 70 years used 2 or more prescription medications. 25 And a 1998 Canadian study of emergency department patients aged 65 years and older found that 91% of the study population was taking at least 1 medication, and the mean number of medications used simultaneously was 4.2 ± 3.1. 8 It is not clear whether our study findings are higher as a result of our methodology, higher use resulting from DoD beneficiaries' access to a generous drug benefit, or the later time period of our study, following several years of unprecedented growth in sales in the pharmaceutical industry. 26 Most likely, all these factors contributed to higher estimates of multiple medication use among the population in the current study.
Consistent with other studies, we found that cardiovascular drugs were the most commonly used medications among older adults, and cardiovascular medication users were the largest overall consumers of medication in the study population. 9 Heart failure, for example, has been characterized as a condition that, to be effectively managed, requires multiple medications, but it is also associated with overuse of ineffective medications for concomitant conditions. 27,28 In a case study of a patient diagnosed with heart failure, hypertension, diabetes, and several other comorbidities, the conduct of a critical medication review and 2 years of monitoring resulted in a reduction in the patient' s medication list from 11 to 5. 28 While this intervention was patient-specific, it highlighted the potential for reducing the size of the medication lists for a cardiovascular patient with multiple comorbidities. Other initiatives cited in the literature reported significant a reductions in both the number of medications taken and total monthly prescription costs. 29,30 A strong argument might be made that the prescribing patterns implied by our findings may be generalizable to other insured ambulatory populations of older adults who use prescription medication. Both the DoD population of beneficiaries www.amcp.org Vol. 13

Mean (SE) Rx* Mean (SE) Therapeutic Categories †
aged 65 years and older and the prescribers who treated them were geographically distributed and integrated with the non-DoD population. More than 90% of the study beneficiaries received most, if not all, of their health care services through civilian providers who also treated the general population. Furthermore, there are no data to indicate that this older DoD health care beneficiary population would experience the incidence and progression of disease and the associated need for medication differently from other older adults nationwide.
While it is possible that the absence of benefit caps or periods of noncoverage and relatively small copayments under TRICARE made compliance with their medication regimen more affordable for the DoD beneficiaries aged 65 years and older compared with those who used other plans (or no plan at all), it is unlikely that prescribers treated older DoD beneficiaries differently from other older adults.
Our findings indicate that approximately 73% of the eligible TRICARE beneficiaries used their TRICARE pharmacy benefit during the study period. Findings from the Third National Health and Nutrition Survey indicated that 74% of the respondents aged 65 years and older confirmed recent use of prescription medication. 31 Despite the congruence of these ratios, it is possible that some of the current study population might have obtained a portion of prescription medications from another health care provider during the study period, the result of which would be an understatement of the total number of medications obtained.
Some safeguards are in place to help protect beneficiaries from the risk posed by multiple drug therapies. In July 2001, DoD implemented an online screening tool that reviews a new prescription against all previous prescriptions filled and alerts the dispensing pharmacist to potentially dangerous drug combinations or therapeutic duplication on the patient' s medication list. This screening process occurs automatically at the time the prescription is filled, and is performed for all fills at military pharmacies, network community pharmacies, and the mailorder pharmacy.

Limitations
Our methodology introduced the potential for both overcounting and undercounting medications obtained by individual beneficiaries over the study period. The use of GCN numbers to count medications represents a potential source of overcounting in the number of medications in this study. By counting unique GCN numbers, we may have counted 1 medication as 2 medications if a beneficiary filled prescriptions for different dosages of the same medication. This potential for overcounting medications is likely offset to some extent by the 90-day study period. Although the TRICARE benefit does not permit dispensing greater than a 90-day supply of medication, it is possible that some beneficiaries obtained additional medications outside the 90-day study period or through a pathway not captured in our dataset.

Examination of Multiple Medication Use Among TRICARE Beneficiaries Aged 65 Years and Older
Our date-of-service period from December through February might also have been subject to seasonal variation in medication use. These months of the year have higher overall drug use relative to other months, so our findings may tend to overestimate actual medication use if annualized. On the other hand, most of the medications in this population are taken for chronic conditions and therefore are less susceptible to seasonal variation.
The absence of data for use of over-the-counter medications is another study limitation and contributes to a potentially significant underestimate of total medications obtained by the study population. The elderly are generally the heaviest users of over-the-counter medications, including vitamins, minerals, and herbal remedies, whose use is often not reported by patients unless they are specifically asked about it. 9, 22 A thorough medication review must consider all types of medications used by patients.
Finally, retrospective evaluation of prescription fill data has limitations. The study dataset would not include any prescriptions filled by beneficiaries who used other health insurance (without using TRICARE as a second payer) or no insurance to pay for their medication. Furthermore, pharmacy fill data only permit examination of dispensed medications, which may differ from actual medication consumption by beneficiaries. Beneficiary compliance with their medication regimen and the extent to which beneficiaries were using their medications concurrently are potentially important considerations that cannot be addressed through analysis of pharmacy fill or claims data.

ss Conclusion
In a 90-day period from December 1, 2004, through February 28, 2005, 73% of eligible TRICARE beneficiaries aged 65 years and older used the pharmacy benefit and received an average of 6 unique medications per user in an average of 4 therapeutic categories. Almost half of TRICARE pharmacy benefit users received 6 or more unique medications. Most study beneficiaries, however, received their health care services through either one of the large, DoD-contracted, civilian health care companies or another health plan, such as Medicare, which greatly limits the DoD' s ability to coordinate care rendered by multiple prescribers. Optimizing medication use among its older beneficiaries represents a significant challenge for the DoD, similar to the one faced by many Medicare Part D drug plans that are required to implement their own medication therapy management programs. This was the first of several studies to aid DoD planners in crafting future pharmacy policy and benefit revisions to promote safer and more effective medication therapy for beneficiaries.

FIGURE 2
What is already known about this subject • As the number of medications per person increases, so does the risk of an adverse drug event as well as higher likelihood of inappropriate drug use.

What this study adds
• 73% of eligible TRICARE beneficiaries aged 65 years and older used the pharmacy benefit in a given 90-day period, and almost half obtained 6 or more unique medications from 4 or more therapeutic categories.